NIAMS Clinical Trial Working Group: Recommendations to Advisory Council

Overview

The NIAMS Clinical Trial Working Group was established to consider how the institute could optimally solicit and fund applications for clinical trials that would have the greatest impact in improving clinical outcomes, whether of rare or common diseases, for people with diseases and/or conditions within the NIAMS mission. Please note that these are recommendations that NIAMS will consider as the institute examines its clinical trials portfolio. 

Summary of Work

  • Timeline: 18 months 
  • Comprehensive review of NIAMS portfolio, including clinical trial mechanisms, number of applications, percent funded, and trends over years.
  • Presentations by, and discussions with, multiple NIH institutes.
  • Extensive discussions led to developing recommendations and reaching consensus. 
  • Expert guidance provided by NIAMS facilitators and support staff.

Key Questions 

NIAMS Director Lindsey A. Criswell, M.D., M.P.H., D.Sc., posed the following key questions for the working group to consider:

Trial Impact:

  1. What types of studies will have the greatest impact on people’s lives?
  2. What is the NIAMS niche in the context of the broader clinical trials landscape?

Investigator/Community Engagement:

  1. Should NIAMS solicit topics to prioritize from the extramural community?
  2. How can NIAMS better support applicants?

Trials Budget/Trial Size Tradeoffs:

  1. What is an appropriate budget ceiling?
  2. Should NIAMS support fewer trials with larger budgets or continue to support a broader mix of trials?

Additional questions considered:

Structure of NIAMS Clinical Trials Program:

  1. How might NIAMS structure its programs to lead impactful trials?

Clinical Trial Network:

  1. Should NIAMS explore establishing or facilitating a clinical trials network?

Clinical Trial Enrollment Diversity:

  1. How can NIAMS support diversity in clinical trial enrollment?

Incorporating the Voices of Those with Lived Experience

  1. How can NIAMS engage those with lived experience to ensure that trials benefit patients?

After extensive internal deliberations, the work group developed interim recommendations that were shared with the NIAMS Advisory Council on August 29, 2023, and later presented new recommendations to the Advisory Council on May 29, 2024.

Interim Recommendations: August 29, 2023

The work group made two interim recommendations during the August 29, 2023, NIAMS Advisory Council Meeting (see videocast starting at 2:38.32) to address following question: How might NIAMS structure its programs to lead to impactful trials?

Recommendation 1:

Consider different options for smaller, exploratory/ feasibility clinical trial mechanisms that allow for larger budgets and extended timeframes.

Maintain the small trial mechanism but allow more flexibility in time, budget, and page length limit.

Response:

NIAMS has developed and published a new R61 small exploratory trials notice of funding opportunity (NOFO) to replace the R21 exploratory trials NOFO.  The direct cost cap was increased to $600K over a three-year period.
 

Recommendation 2:

Consider establishing a two-phase, milestone-based awards process, using the UG3/UH3 mechanism, for large clinical trial applications.

Response:

NIAMS has developed and published a new UG3/UH3 phased clinical trials NOFO: PAR-24-208.

New Recommendations: May 29, 2024

The work group presented recommendations during the May 29, 2024, NIAMS Advisory Council Meeting (see videocast starting at 2:37.21).

Trial Impact

1. What types of clinical trials will have the greatest impact on people’s lives?

Recommendations: 

  • Consider shifting the institute's strategy from maximizing the number of funded trials to funding the most impactful trials. 
  • Prioritize clinical trials that emphasize the impact of an intervention, taking into consideration effect size and burden of disease both at the individual and population levels 
  • Align with relevant professional and patient communities to best understand these stakeholders’ views of their biggest unmet needs. 
  • Consider a formal role for Council as a second level of review to better assess trial impact.

Rationale: 

  • Study sections score the science/methodology; a second review would score for impact.
  • NIAMS Council is optimally positioned to conduct the second-level review.

Suggested Process: 

  • Council will review clinical trial applications greater than $500,000 at the closed session of Council meetings and vote on their approval.

2. What is the NIAMS niche in the context of the broader clinical trials landscape?

Recommendations: 

  • Emphasize studies that advance and/or impact clinical management and guidelines.
  • The institute’s unique niche is looking at areas that are not funded by industry.
  • Consider a trial selection process with specific criteria in the RFA for “game-changing” research.

Investigator/Community Engagement

3. Should NIAMS solicit topics to prioritize from the extramural community?

Recommendations: 

  • Seek input in the full range of areas of the NIAMS mission, from a broad array of stakeholders.
  • Interactions with community groups should be bi-directional and obtained in a coordinated and sustained fashion.
  • Identify and publish key areas of interest and support investigators pursuing novel approaches to address research gaps.
  • NIAMS areas of interest can be listed on the NIAMS website as well as in Notices of Special Interest (NOSIs) and Requests for Application (RFAs).

4. How can NIAMS better support clinical trial applicants?

Recommendations: 

  • Develop and promote informational and educational initiatives, including:
    • Encourage applicants to communicate early with program directors.
    • Conduct webinars and other forms of communication for new clinical trials funding opportunities. 
    • Provide tools for investigators, such as a list of lessons learned (best practices); tools to set up and manage data repositories; and a compilation of sites interested in participating in clinical trials.
    • Develop guidance for investigators on funding partnerships.
  • Expand NIAMS scope and oversight:
    • Expand the scope of the AMSC study section to include other clinical studies (e.g., larger observational studies where clinical trials are not feasible).
    • Define and further expand Program staff roles in clinical trials oversight: establish sub-specialty teams of Program Directors to oversee trials based on trial type (drug, surgical, and behavioral); and add more MDs to the Program Director staffing pool.
  • Evaluate and identify the most impactful clinical trial designs. 
  • Provide educational resources for FDA regulated studies.

Trials Budget/Trial Size Tradeoffs:

5. What is an appropriate budget ceiling? 

6. Should NIAMS support fewer trials with larger budgets or continue to support a broader mix of trials? 

Recommendations: 

  • Continue to support a broad mix of clinical trials mechanisms including a range of budget totals and trial durations.
  • Consider re-issuing a funding opportunity for a clinical trial planning grant that focuses on an earlier phase of trial planning than the UG3 and that includes impact as a review criterion.

NOTE: The committee noted that recommendations should not focus on the how NIAMS determines the funding threshold or the budget ceiling for clinical trials.

Clinical Trials Network

7. How might NIAMS structure its programs to lead to impactful trials?

8. Should NIAMS explore establishing or facilitating a clinical trials network?

Recommendations:

  • Given NIAMS’ broad mission area and limited budget, consider whether there are components of an existing Clinical Trials Network or Clinical and Translational Science Awards (CTSA) that could be adopted to support investigators and would provide economies of scale and reduce effort.
  • Potential components could include, but are not limited to, centralized data coordinating centers; data collection; support for recruitment and Data, Safety, and Monitoring Boards; Institutional Review Boards; community advisory boards; navigator networks; data sharing resources; regulatory support; and clinical trial design.

Rationale:

  • Reinventing the wheel for every clinical trial is inefficient and costly. 
  • De novo development of all necessary trial elements and infrastructure is an overwhelming experience for a first time clinical trialist which may diminish enthusiasm to pursue a trial application.

Clinical Trials Enrollment Diversity

9. How can NIAMS support diversity in clinical trial enrollments?

  • To improve recruitment and retention of understudied populations in clinical trials, NIAMS should develop a list of interested sites with expertise in community engagement and make that list available to grantees seeking to partner with those sites.
  • Offer more training for Scientific Review Officers (SROs) and reviewers on how to evaluate applications to integrate enrollment approaches to increase diversity. NIAMS should facilitate diversity in enrollment by:
    • Sharing options, lessons learned, and best practices.
    • Sharing approaches from different institutions.
    • Sharing approaches on recruitment of people from different cultures.
    • Guiding applicants to resources on best practices.
    • Outlining guidance on budgeting for these activities.

Incorporating the Voices of Those with Lived Experience

10. How can NIAMS engage those with lived experience to ensure that trials benefit patients?

Recommendations:

  • Encourage engagement of individuals with lived experience in the design, implementation, and dissemination of clinical trials.
  • Extend engagement to current participants in active clinical trials, which could potentially include:
    • Recruitment, retention, and awareness
    • Reporting of summary results
    • Return of individual results (if appropriate)
    • Preparation of updates on trial progress

Work Group Membership

  • Co-Chairs
    • Joan Bathon, M.D., Columbia University
    • Stuart Goodman, M.D., Ph.D., Stanford University
  • Orthopaedics
    • Joshua Jacobs, M.D., Rush Medical College
    • Kurt Spindler, M.D., Cleveland Clinic – Florida Region
  • Patient Advocates
    • Tiffany Westrich-Robertson, International Foundation for Autoimmune & Autoinflammatory Arthritis (AiArthritis)
  • Rheumatology
    • Peter A. Merkel, M.D., MPH, University of Pennsylvania
    • Maria Suarez-Almazor, M.D., Ph.D., University of Texas MD Anderson Cancer Center
  • Skin
    • Eric Simpson, M.D., MCR, Oregon Health & Science University
  • Muscle
    • Paula Clemens, M.D., University of Pittsburgh
  • Bone
    • Sundeep Khosla, M.D., Mayo Clinic
    • Cliff Rosen, M.D., Maine Medical Center
  • Pain / Biobehavioral / Rehab
    • Greg Hicks, PT, Ph.D., University of Delaware
    • Christine Rini, Ph.D., Northwestern University
  • NIH NIAMS Facilitators and Staff Support
    • Robert Carter, M.D., Deputy Director
    • Shahnaz Khan, Ph.D., MPH, Former Branch Chief, Clinical Research Operations 
    • Charles Washabaugh, Ph.D., Program Director Orthopaedic Research
    • Dandre Thornhill, Ph.D., Branch Chief, Clinical Research Operations
    • Darren Sledjeski, Ph.D., Director, Division of Extramural Activities
    • Tanisha Brown-Caines, MBA, Clinical Research Manager
    • Tom Bond, Senior Advisor

For more information, please email [email protected]. 

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